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Genome-wide profiling of normal gastric mucosa identifies Helicobacter pylori- and cancer-associated DNA methylome changes.

Abstract：

:The large geographic variations in the incidence of gastric cancer (GC) are likely due to differential environmental exposures, in particular to Helicobacter pylori (H. pylori) infection. We aimed to investigate the impact of H. pylori on the epigenome in normal gastric mucosa and methylation changes associated with cancer risk independent of H. pylori. A discovery set of normal gastric mucosa from GC cases (n = 42) and controls (n = 42), nested in a large case-control study and stratified by H. pylori status, were subjected to genome-wide methylation profiling. Single-nucleotide polymorphism arrays from peripheral blood leukocytes were used to conduct methylation quantitative trait loci (mQTL) analysis. A validation set of gastric mucosa samples (n = 180) was used in the replication phase. We found 1,924 differentially methylated positions (DMPs) and 438 differentially methylated regions (DMRs) associated with H. pylori infection, most of which were hypermethylated. Significant methylation alterations identified in the initial set were successfully replicated. Furthermore, the H. pylori-associated DMP/Rs showed marked stability ('epigenetic memory') after H. pylori clearance. Interestingly, we found 152 DMRs associated with cancer risk independent of the H. pylori status in normal gastric mucosa. The methylation score derived from three biomarkers was a strong predictor of GC. Finally, the mQTL analysis indicated that the H. pylori- and cancer-specific methylation signatures were minimally affected by genetic variation. The comprehensively characterized methylome changes associated with H. pylori infection and GC risk in our study might serve as potential biomarkers for early cancer progression in tumour-free gastric mucosa.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Woo HD,Fernandez-Jimenez N,Ghantous A,Degli Esposti D,Cuenin C,Cahais V,Choi IJ,Kim YI,Kim J,Herceg Z

doi

10.1002/ijc.31381

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

597-609

issue

eissn

0020-7136

issn

1097-0215

journal_volume

143

pub_type

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Genome-wide profiling of normal gastric mucosa identifies Helicobacter pylori- and cancer-associated DNA methylome changes.